The fundamental mission of academic medicine is the acquisition and application of scientific knowledge to improve health care. In order for the medical enterprise to function effectively, it is critically important for the academic biomedical community to have physician-scientists who receive special training that integrates both a rigorous scientific education with state-of-the-art medical education. These individuals facilitate interactions between the clinic and lab that promote both basic investigation on disease mechanisms and translational research leading to clinical applications. Thus, they are positioned to be leaders in biomedical research and educational communities. In this MSTP application, we describe The Ohio State University (OSU) Medical Scientist Program (MSP), whose objective is to provide MD-PhD trainees with the rigor, depth, and breadth of both scientific and medical education in a way that facilitates integrating both sets of training to prepare them for careers as successful physician-scientists. In order to achieve these goals, the MSP serves as a partnership program linking an innovative medical school curriculum with three integrated graduate programs to allow students to pursue in-depth scientific inquiry in a wide variety of areas. Medical school coursework is completed using OSU's Independent Study Program, a unique classroom- independent course of study which enables students to use structured objectives and distributed sources of information to learn the pre-clinical medical curriculum. At the same time, students begin their PhD training by taking graduate courses in one of three specific programs, the Integrated Biomedical Science Graduate Program (IBGP), the Neuroscience Graduate Studies Program (NGSP), or Biomedical Engineering (BME). By beginning coursework in both areas simultaneously, students receive much better integration of content than would be achieved by studying the material sequentially. In addition, this engineered integrated approach means that students have completed nearly all their coursework by the end of two years in the program. Beginning in the third year, students can devote the bulk of their time to their dissertation research, enabling them to complete their studies in a time-efficient manner typically lasting 8 years. This highly integrated MD-PhD program has attracted interest from a large pool of excellent applicants for the 5 positions that we fill annually. We are requesting funds for 30 student years of funding over 5 years beginning with 2 in the first year and adding 2 each year to a total of 10 in year 5. Recognition of our program by NIGMS will allow us to recruit the best and brightest students, enhancing the ability of the MSP to train the future leaders who will enable the Ohio State University College of Medicine to achieve its stated mission: To improve people's lives through innovation in research, education and patient care. PUBLIC HEALTH RELEVANCE: The mission of all NIH-funded research is the improvement of this nation's health. Since MD-PhD trainees have expertise in the continuum of basic science to clinical application, they have the optimal skill set to discover fundamental disease mechanisms and to bring these findings back to the clinic. Thus, students dedicated to pursuing this career path should be nurtured and placed in training environments such as the Ohio State University that will enable them to reach these lofty goals. NIGMS support of this training is essential in providing the environment that will allow these future physician-scientist leaders to flourish.